Formation and seeding of amyloid fibrils from wild-type hen lysozyme and apeptide fragment from the beta-domain

Wild-type hen lysozyme has been converted from its soluble native state int o highly organized amyloid fibrils. Ln order to achieve this conversion, co nditions were chosen to promote partial unfolding of the native globular fo ld and included heating of low-pH solutions and addition of organic solvent s. Two peptides derived from the beta-sheet region of hen lysozyme were als o found to form fibrils very readily. The properties and morphologies of th e amyloid fibrils formed by incubation either of the protein or the peptide s are similar to those produced from the group of proteins associated with clinical amyloidoses. Fibril formation by hen lysozyme was substantially ac celerated when aliquots of solutions in which fibrils of either one of the peptides or the full-length protein had previously formed were added to fre sh solutions of the protein, revealing the importance of seeding in the kin etics of fibril formation. These findings support the proposition that the beta-domain is of particular significance in the formation of fibrils from the full-length protein and suggest similarities between the species giving rise to fibril formation and the intermediates formed during protein foldi ng. (C) 2000 Academic Press.